Mechanosensitive ion channels (MCSs) were discovered in tissue cultured skeletal muscle cells using single channel patch clamp recording and have since been found in both the plant and animal kingdoms and in the cells of most tissues. Most of them open with increasing membrane tension [stretch-activated channels (SACs)], but a few are tonically active and close with increasing tension [stretch-inactivated channels (SICs)]. In at least one case, the channels are also sensitive to the sign of the patch curvature. In animal cells, the channels tend to display selectivity for either generic cations or potassium. MSCs form a family that is generally distinct from known channels families, i.e. most channels are not mechanically sensitive.
Ion selectivity of the MSC channel family is variable, as in the case of voltage-activated or ligand-activated channel families. In the animal cells, the most common forms are cation selective and, more particularly, potassium selective. The cation channels will pass divalents such as Ca.sup.+2 and Ba.sup.+2 as well as monovalents. Due to their ability to pass Ca.sup.+2, effects of cationic MSCs are potentially complicated. Even under voltage clamp conditions, incoming Ca.sup.+2 may activate other channels, such as Ca.sup.2+ activated Cl.sup.-- channels, a link that has been invoked in the regulation of cell volume.
Investigations of spider venoms for identification of biological entities with commercial potential has focused primarily on the agrochemical sector. The ultimate goal of these activities has been the search for chemical constituents which interact selectively with invertebrate species to induce paralysis and or death with minimal mammalian toxicological properties. However in recent years, spider venoms have joined the other predator-derived venoms being exploited for identification of compounds which identify mammalian targets and which assist the development of pharmaceuticals. The arachnid species Grammostola spatulata, commonly referred to as the Chilean pink tarantula spider, is a member of the Theraphosidae family and the Chelicerata order. Previous studies by Lampe et al. (1993) Molecular Pharmacology 4:451-460 showed that venom of G. spatulata contains a peptide which interacts in a non-selective manner with voltage-sensitive calcium channels.
Ventricular fibrillation is a frequent cause of sudden death in the United States and Europe. It has been suggested that abnormal mechanical factors induce electrophysical changes conducive to arrhythmia via "mechanoelectric feedback". Sarcolemma stretch-activated channels have been postulated as a mechanism of mechanoelectric feedback and they may play a role in the genesis of stretch-activated arrhthymias.